The main objective of this research proposal is to determine the efficacy of recombinant human lactoferrin (hLF) to treat gastrointestinal disorders induced by Helicobacter pylori infection or NSAID toxicity. These two factors are responsible for >90% of all gastric and duodenal ulcers. H. pylori infection of this stomach is responsible for chronic gastritis, peptide ulcer disease, and some forms of gastric cancer. NSAIDs such as aspirin are widely used for a variety of actions, but suffer from limiting side effects on the stomach such as bleeding and ulceration. The approach taken in this proposal is to study animal models of Helicobacter infection (mouse) or NSAID injury (rat) in order to assess the in vivo effectiveness of hLF. Mice infected with H. pylori, or the mouse-adapted strain, H. felis, will be studied to determine the efficacy of hLF at reversing or clearing the infection. Chronically H. felis-infected mice, which are a model for gastric atrophy and an increased risk of gastric cancer, will be investigated for the ability of hLF to reverse atrophic changes. Finally, the ability of hLF to heal gastro-duodenal mucosa will be assessed in rats models of chemically- induced gastric or duodenal injury. These studies will provide evidence to support clinical trials to hLF, and may result in 1) better treatments for H. pylori infection than are currently available with fewer side effects and less risk for development of antibiotic-resistant bacterial strains and 2) new treatment for NSAID-induced toxicity which will allow greater use of this important class of drugs. PROPOSED COMMERCIAL APPLICATION: Human lactoferrin may be effective in the treatment of H. pylori infection which is the causative infectious agent in chronic gastritis, peptide ulcer disease, and some gastric cancers. Lactoferrin may also promote healing in NSAID-induced gastric injury.